This study aimed to investigate the progress of wound healing around silicone expander with particular emphasis on fibroblasts, myofibroblasts and collagen in the repair phase. Semi-quantitative evaluation of inflammatory cells and their cytokines, fibroblasts and myofibroblasts at the tissue-material interface was carried out. Commercially available silicone expander was implanted in gluteus muscle of young female Wistar rats for 3, 7, 14, 30, 90 and 180 days. Ultra high molecular weight polyethylene served as control. The cellular response was studied by immunohistochemistry and Transmission Electron Microscopy. A thick collagenous fibrous capsule was observed around the silicone expander at 180 days, with persistent myofibroblasts, lymphocytes and macrophages as compared to the thin fibrous encapsulation around the UHMWPE implants. The regulatory role of cytokines and immune cells in myofibroblast persistence in tissue-implant interface around silicone expander has been extensively studied. Results of this study indicate the need to elucidate the signaling molecules in the transition of fibroblast to myofibroblast around silicone expander implants.

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The excessive collagen deposition around silicone breast implants followed by contracture and development of severe pain is a major clinical problem. This study was conducted to investigate the profibrotic and antifibrotic cytokines secreted by inflammatory cells and development of myofibroblasts at the tissue material interface around silicone breast expander and ultra-high-molecular-weight polyethylene (UHMWPE). Both materials were implanted in rats for 30, 90 and 180 days. Inflammatory cells and collagen deposition at the material-tissue interface were assessed with Haematoxylin-Eosin and Masson's Trichrome stain. Gene expression of TGFbeta, IL-1beta, IFNgamma, IL10 and alpha-SMA was quantitated by real-time (RT)-PCR in the peri-implant tissue. Results indicate a difference in collagen deposition and myofibroblast development around both materials with involvement of TGFbeta, IFNgamma and IL10. The results emphasise the need for further investigation into the molecular mechanisms of protomyofibroblast and myofibroblast formation around silicone implants, which would provide information on these target cells for inhibitory therapy in the clinical situation.

Materials used for medical devices are usually tested for their biocompatibility, before use. However, it is known that long-term implantation in the body may lead to degradation of the material leading to an adverse tissue response. The failure of silicone breast implants due to excessive fibrosis and contracture has led to studies to delineate the cause of fibrosis around this material. To detect the biological moieties involved, conditioned media from RAW 264.7 macrophages seeded over commercially available silicone tissue expander material was added to L929 fibroblasts. Ultrahigh-molecular-weight polyethylene and tissue culture grade polystyrene served as the control materials. The gene expression of fibrogenic cytokines, interleukin-6 (IL-6), and transforming growth factor beta (TGFβ) in the RAW macrophages and myofibroblast marker alpha smooth muscle actin (αSMA) in L929 cells were quantitated by real time polymerase chain reaction. Protein expression analysis of αSMA was carried out by immunocytochemical staining and confocal microscopy. An in vitro degradation study of silicone expander material in pseudoextracellular fluid (PECF) and the αSMA expression in fibroblasts incubated with the silicone extract containing PECF has revealed the role of silicone leachants in induction of myofibroblasts. This in vitro expression study revealed the additional profibrotic role of IL-6 in fibroblast to myofibroblast transition and the synergy between material aspects and biomolecules in regulating fibrosis around Silicone implants. These findings may help in targeting newer biological moieties in the profibrotic pathway and in devising better manufacturing processes aiding the life of millions of patients.

Severe capsular contracture around silicone expander breast implants leading to pain and failure is a major clinical problem. Even though earlier studies have implicated the immunogenicity of silicone, the role of physical and chemical properties of the silicone material in excessive collagen deposition and fibrosis has been less addressed. The present study investigates whether there is any correlation between the type of curing systems i.e. addition and free radical curing and the fibrosis around silicone elastomer. The experiment carried out uses commercially available silicone ventriculo-peritoneal shunt material elastomer cured by platinum and the results are compared with results obtained in a similar study carried out by the authors using commercially available silicone tissue expander material cured by peroxide. Ultra-high molecular weight poly-ethylene (UHMWPE), the standard reference for biocompatibility evaluation, was used as the control material. The materials were implanted in rat skeletal muscle for 30 and 90 days. Inflammatory cells, myofibroblasts, cytokines, and collagen deposition at the material-tissue interface were identified by haematoxylin-eosin and Masson's Trichrome stains and semi-quantitated based on immunohistochemical studies. Results indicate that even though the cellular response in the initial phase of wound healing was similar in both platinum and peroxide-cured materials, the collagen deposition in the proliferative phase was more around peroxide-cured material in comparison to the platinum-cured silicone elastomer. There is a need to look into the molecular mechanisms of this interaction and the possibility of using curing systems other than free radical peroxide in the manufacture of silicone elastomer expanders for breast prosthesis.